Hemopoiesis is a major dose limiting normal function necessary to preserve when administering radiation and/or chemotherapy alone or in combination. These investigations are concerned with understanding and possibly altering the response of the hematopoietic progenitor compartment in order to improve the therapeutic ratio. The specific phenomena to be studied are: recruitment of hematopoietic stem cells into cycle; dose fractionation of x-ray, drugs, or their combination; and interaction or potentiation of x-ray by drugs or antisera. All studies will be done using the mouse. We will employ the spleen colony assay primarily and, to a lesser extent, the granulocyte and erythrocyte repopulating abilities. Current therapy for malignant disease is becoming more complicated. Treatment can kill stem cells, recruit others into cycle, partially synchronize them and alter patterns of differentiation. These will have differing consequences on the effect of therapies given in multiple fractions and in combination and can profoundly affect the therapeutic ratio. The undersigned agrees to accept responsibility for the scientific and technical conduct of the project and for provision of required progress reports if a grant is awarded as the result of this application.